ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.890_899del (p.Leu297fs)

dbSNP: rs1555602141
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569137 SCV000671900 pathogenic Hereditary cancer-predisposing syndrome 2023-05-03 criteria provided, single submitter clinical testing The c.890_899del10 pathogenic mutation, located in coding exon 6 of the RAD51C gene, results from a deletion of 10 nucleotides at nucleotide positions 890 to 899, causing a translational frameshift with a predicted alternate stop codon (p.L297Hfs*2). This alteration has been identified in a cohort of 2649 consecutive cases of breast and/or ovarian cancer and in an individual diagnosed with prostate cancer (Golmard L et al. Eur. J. Hum. Genet., 2017 12;25:1345-1353; Paulo P et al. PLoS Genet., 2018 04;14:e1007355). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV000576176 SCV000676964 pathogenic Fanconi anemia complementation group O 2024-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu297Hisfs*2) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 25980754, 29255180, 29659569). ClinVar contains an entry for this variant (Variation ID: 484744). Studies have shown that this premature translational stop signal is associated with inconclusive levels of altered splicing (internal data). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000576176 SCV001140726 pathogenic Fanconi anemia complementation group O 2019-05-28 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000569137 SCV001347925 pathogenic Hereditary cancer-predisposing syndrome 2023-10-01 criteria provided, single submitter clinical testing This variant deletes 10 nucleotides in exon 6 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in one individual each affected with ovarian cancer (PMID: 29255180), breast and ovarian cancer (PMID: 33326660), bladder and prostate cancer (PMID: 29659569) and an individual affected with Lynch syndrome-associated cancer and/or polyps (PMID: 25980754). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Molecular Oncology Research Center, Barretos Cancer Hospital RCV000709516 SCV001438607 pathogenic Hereditary breast ovarian cancer syndrome 2020-08-01 criteria provided, single submitter research
Sema4, Sema4 RCV000569137 SCV002530028 pathogenic Hereditary cancer-predisposing syndrome 2021-12-20 criteria provided, single submitter curation
GeneDx RCV003314621 SCV004014214 pathogenic not provided 2023-06-16 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25980754, Monteiro2019[MtgAbstract], 29659569, Cardoso2018[Thesis], 27535533, Teixeira2023[preprint], 33258288, 35264596, 33326660, 29255180, 36119527)
Baylor Genetics RCV003459371 SCV004208015 pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2024-03-22 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV003459371 SCV004933029 pathogenic Breast-ovarian cancer, familial, susceptibility to, 3 2024-01-03 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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